Angiogenesis, which is the proliferation and directed growth of capillary endothelium, along with fibroplasia and collagen synthesis are integral components of a host's response to wounding. The activation of platelets and the clotting cascade are among the first reactions to injury.
Platelets activated by thrombin release a mitogen, or growth factor, for fibroblasts and smooth muscle cells and stimulate increased collagen synthesis by smooth muscle cells in vitro. The mitogen (platelet-derived growth factor, hereinafter PDGF) is composed of two polypeptides. An article describing PDGF was published in 1982 by G. R. Grotendorst, T. Chang, H. E. J. Seppa, H. K. Kleinman and G. R. Martin in the Journal of Cellular Physiology entitled "Platelet-Derived Growth Factor is a Chemoattractant for Vascular Smooth Muscle Cells", Vol. 113, pp. 261-266. The article is incorporated herein by reference.
A non-mitogenic substance, called angiogenic factor, is also produced by thrombin-activated platelets and stimulates capillary growth. Various angiogenesis factors are known including tumor, retinal and wound fluid angiogenesis factors. It is unknown whether all angiogenesis factors share a common mechanism of action upon capillary endothelial cells.
Angiogenesis factors were isolated and described Proc. Nat'l Acad. Sci. U.S.A. (7773-7777, Dec. 1982), in an article entitled "Isolation of a nonmitogenic angiogenesis factor from wound fluid," the disclosure of which is incorporated herein by reference.
Angiogenesis and platelet-derived growth factors are described by D. R. Knighton, T. K. Hunt, K. K. Thakral and W. H. Goodson III, in "Role of Platelets and Fibrin in the Healing Sequence", Annals of Surgery 196: 379-388 (1982), the disclosure of which is incorporated by reference. In this article, the successful treatment of a non healing wound in a patient is described in which a single, ten-unit platelet transfusion was given. The wound healed in three weeks.
A recent study has indicated that when the body's normal healing process works, it is only at about a 50% effectiveness level.
A human angiogenic factor is produced from human foreskin fibroblasts in U.S. Pat. No. 4,273,871 to Tolbert, et al. A publically available foreskin fibroblast cell line is utilized to produce an angiogenic factor.
In U.S. Pat. No. 4,479,896 to Antoniades, the disclosure of which is incorporated herein by reference, platelet derived growth factors are characterized and extracted for study by gel electrophoresis means.